2. Academic Validation
  3. IL-1β augments TGF-β inducing epithelial-mesenchymal transition of epithelial cells and associates with poor pulmonary function improvement in neutrophilic asthmatics

IL-1β augments TGF-β inducing epithelial-mesenchymal transition of epithelial cells and associates with poor pulmonary function improvement in neutrophilic asthmatics

  • Respir Res. 2021 Aug 3;22(1):216. doi: 10.1186/s12931-021-01808-7.
Shengding Zhang  # 1 2,  Yu Fan  # 3,  Lu Qin 1 2,  Xiaoyu Fang 1 2,  Cong Zhang 1 2,  Junqing Yue 1 2,  Wenxue Bai 1 2,  Gang Wang 4,  Zhihong Chen 5,  Harld Renz 6 7,  Chrysanthi Skevaki 6 7,  Xiansheng Liu 8 9 10,  Min Xie 11 12 13
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Key Laboratory of Respiratory Diseases, National Ministry of Health of the People's Republic of China and National Clinical Research Center for Respiratory Disease, Wuhan, China.
  • 3 Department of Respiratory and Critical Care Medicine, Qiandongnanzhou People's Hospital, Kaili, China.
  • 4 Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, China.
  • 5 Department of Respiratory and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 6 Institute of Laboratory Medicine, Philipps Universität Marburg, Marburg, Germany.
  • 7 Universities of Giessen and Marburg Lung Center (UGMLC), and the German Center for Lung Research (DZL), Marburg, Germany.
  • 8 Department of Respiratory and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China. doctorliu69@126.com.
  • 9 Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. doctorliu69@126.com.
  • 10 Key Laboratory of Respiratory Diseases, National Ministry of Health of the People's Republic of China and National Clinical Research Center for Respiratory Disease, Wuhan, China. doctorliu69@126.com.
  • 11 Department of Respiratory and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China. xie_m@126.com.
  • 12 Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. xie_m@126.com.
  • 13 Key Laboratory of Respiratory Diseases, National Ministry of Health of the People's Republic of China and National Clinical Research Center for Respiratory Disease, Wuhan, China. xie_m@126.com.
  • # Contributed equally.
PMID: 34344357 DOI: 10.1186/s12931-021-01808-7
Abstract

Background: Neutrophilic asthmatics (NA) have less response to inhaled corticosteroids. We aimed to find out the predictor of treatment response in NA.

Methods: Asthmatics (n = 115) and healthy controls (n = 28) underwent clinical assessment during 6-month follow-up with standardized therapy. Asthmatics were categorized by sputum differential cell count. The mRNA expressions were measured by RT-qPCR for sputum cytokines (IFN-γ, IL-1β, IL-27, FOXP3, IL-17A, and IL-5). The protein of IL-1β in sputum supernatant was detected by ELISA. Reticular basement membranes (RBM) were measured in the biopsy samples. The role and signaling pathways of IL-1β mediating the epithelial-mesenchymal transition (EMT) process were explored through A549 cells.

Results: NA had increased baseline sputum cell IL-1β expression compared to eosinophilic asthmatics (EA). After follow-up, NA had less improvement in FEV1 compared to EA. For all asthmatics, sputum IL-1β mRNA was positively correlated with protein expression. Sputum IL-1β mRNA and protein levels were negatively correlated to FEV1 improvement. After subgrouping, the correlation between IL-1β mRNA and FEV1 improvement was significant in NA but not in EA. Thickness of RBM in asthmatics was greater than that of healthy controls and positively correlated with neutrophil percentage in bronchoalveolar lavage fluid. In vitro experiments, the process of IL-1β augmenting TGF-β1-induced EMT cannot be abrogated by glucocorticoid or montelukast sodium, but can be reversed by MAPK inhibitors.

Conclusions: IL-1β level in baseline sputum predicts the poor lung function improvement in NA. The potential mechanism may be related to IL-1β augmenting TGF-β1-induced steroid-resistant EMT through MAPK signaling pathways.

Trial registration: This study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (IRB ID: 20150406).

Keywords

Asthma; Epithelial-mesenchymal transition; IL-1β; Pulmonary function; TGF-β1.

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